cofirasersen (IONIS-ENAC-2.5Rx) / Ionis, Cystic Fibrosis Foundation - LARVOL DELTA

Randomised, phase 1/2a trial of ION-827359, an antisense oligonucleotide inhibitor of ENaC. (PubMed, ERJ Open Res) - "The tolerability and safety of ION-827359 appear favourable at this stage of investigation. Reduction in ENaC mRNA supports mechanistic efficacy at the doses and regimens tested, and supports further investigation of ION-827359 in pwCF."

Journal • P1/2 data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Safety and Tolerability Demonstrated with Inhaled αENaC Antisense Oligonucleotide (ION-827359) in Patients with Cystic Fibrosis (ATS 2021) - "These results demonstrate strong evidence of tolerability and safety at the doses and regimens tested and supports further investigation of ENaC ASO ION-827359 in patients with cystic fibrosis."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB) (clinicaltrials.gov) - P2a; N=60; Terminated; Sponsor: Ionis Pharmaceuticals, Inc.; N=180 ➔ 60; Trial completion date: Sep 2021 ➔ Apr 2021; Recruiting ➔ Terminated; Business Decision to Terminate Study

Clinical • Enrollment change • Trial completion date • Trial termination • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Ionis reports fourth quarter and full year 2020 financial results and recent business achievements (PRNewswire) - "Q4 2020 and Recent Pipeline Highlights....Unlocked potential new pulmonary disease franchise with positive IONIS-ENAC-2.5Rx data....Advanced IONIS-ENAC-2.5Rx into Phase 2 development in patients with chronic obstructive pulmonary disease (COPD)....Anticipated 2021 Data Readouts: IONIS-ENAC-2.5Rx - Phase 2 - Cystic fibrosis - H1....Anticipated 2021 Study Initiations: IONIS-ENAC-2.5Rx - Phase 2 - Cystic fibrosis not amenable to CFTR modulators - H2."

New P2 trial • P2 data • Trial status • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Respiratory Diseases

A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis (clinicaltrials.gov) - P1/2; N=98; Completed; Sponsor: Ionis Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Oct 2020; Trial primary completion date: Jun 2020 ➔ Oct 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB) (clinicaltrials.gov) - P2a; N=180; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

Ionis reports third quarter 2020 financial results and recent business achievements (Ionis Pharmaceuticals Press Release) - "Third Quarter 2020 and Recent Pipeline Highlights: IONIS-FXI-LRx advanced into Phase 2b development in patients with end-stage renal disease...IONIS-ENAC-2.5 Rx Phase 2 study in patients with cystic fibrosis....Dosing completed in the IONIS-ENAC-2.5 Rx Phase 2 study in patients with cystic fibrosis."

Enrollment closed • Trial status • Renal Disease

Ionis’ inhaled antisense medicine demonstrates potential as a novel treatment for cystic fibrosis (PRNewswire) - P1, N=98; NCT03647228; Sponsor: Ionis Pharmaceuticals, Inc.; "Ionis Pharmaceuticals...announced today that data from a clinical trial of IONIS-ENAC-2.5Rx demonstrated a significant decrease in the expression of epithelial sodium channel (ENaC) in healthy volunteers...Data from the Phase 1 study will be presented via e-poster at the 2020 North American Cystic Fibrosis Conference, which will hold virtual sessions and discussions Oct. 21-23....The company also plans to initiate a clinical study to evaluate IONIS-ENAC-2.5Rx in patients with COPD associated with chronic bronchitis starting later this year....The primary endpoint of the study was evaluation of safety and pharmacokinetics of IONIS-ENAC-2.5Rx delivered via a Pari eFlow mesh nebulizer..."

P1 data • Trial initiation date • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Respiratory Diseases

[VIRTUAL] SAFETY, TOLERABILITY, AND TARGET ENGAGEMENT DEMONSTRATED WITH INHALED ENAC ANTISENSE OLIGONUCLEOTIDE (ION-827359) IN A PHASE 1 HEALTHY VOLUNTEER STUDY (NACFC 2020) - "These results demonstrate strong evidence of tolerability and safety at the doses and regimens tested and supports further investigation of ENaC ASO ION-827359 in patients with cystic fibrosis. Furthermore, there was evidence of strong target engagement with this nebulized ASO."

Clinical • P1 data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Respiratory Diseases

Ionis reports second quarter 2020 financial results and recent business achievements (Ionis Pharmaceuticals Press Release) - "Initiate a Phase 2 study of IONIS-ENaC-2.5Rx in patients with chronic obstructive pulmonary disease (COPD)"

New P2 trial • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis (clinicaltrials.gov) - P1/2; N=98; Active, not recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB) (clinicaltrials.gov) - P2a; N=180; Not yet recruiting; Sponsor: Ionis Pharmaceuticals, Inc.

Clinical • New P2a trial • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis (clinicaltrials.gov) - P1/2; N=88; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Trial completion date: Oct 2019 ➔ Jun 2020; Trial primary completion date: Oct 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date

A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis (clinicaltrials.gov) - P1/2; N=88; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Phase classification: P1 ➔ P1/2; N=64 ➔ 88

Clinical • Enrollment change • Phase classification